Phase IV Multi-arm Study of CDK4/6 Pharmacokinetics in Healthy Volunteers With Known CYP3A4*22 Genotype

NCT05691400 | Withdrawn Phase 4 FDA Drug

• 2 other identifiers: UMCC 2022.106HUM00220623
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The objective of this study is to estimate the effect of CYP3A4\*22 on the clearance and area under the plasma concentration-time curve of Palbociclib, Ribociclib, and Abemaciclib

Conditions

CYP3A4*22

Outcome Measures

Primary Outcomes (3)

• Effect of CYP3A4*22 on the Clearance of Palbociclib

  To determine the effect of CYP3A4\*22 on the Clearance of Palbociclib when administered as a single dose to healthy volunteers.

  2 days after initiation of Palbocicblib treatment

• Effect of CYP3A4*22 on the Clearance of Ribociclib

  To determine the effect of CYP3A4\*22 on the Clearance of Ribociclib when administered as a single dose to healthy volunteers.

  up to 32 days after initiation of Study drug

• Effect of CYP3A4*22 on the CL of Abemaciclib

  To determine the effect of CYP3A4\*22 on the Clearance of Abemaciclib when administered as a single dose to healthy volunteers.

  up to 62 days after initiation of Study drug

Study Arms (3)

CYP3A4*1/*1

EXPERIMENTAL

This arm will include subjects with CYP3A4\*1/\*1 genotype. They will receive a single oral dose of each CDK4/6 inhibitor on separate days, with at least 6 days and no more than 30 days between each medication. All participants will receive the medications in the same order: Palbociclib, Ribociclib, Abemaciclib Ribociclib- 200 mg tablet Abemaciclib- 150 mg tablet Palbociclib-125 mg tablet PK sampling will be done at the time of drug administration and at different time points until 48 hours post administration.

Drug: Palbociclib 125Mg Tab; Drug: Ribociclib 200Mg Oral Tablet; Drug: Abemaciclib 150 MG Oral Tablet

CYP3A4*1/*22

EXPERIMENTAL

This arm will include subjects with CYP3A4\*1/\*22 genotype. They will receive a single oral dose of each CDK4/6 inhibitor on separate days, with at least 6 days and no more than 30 days between each medication. All participants will receive the medications in the same order: Palbociclib, Ribociclib, Abemaciclib Ribociclib- 200 mg tablet Abemaciclib- 150 mg tablet Palbociclib-125 mg tablet PK sampling will be done at the time of drug administration and at different time points until 48 hours post administration.

Drug: Palbociclib 125Mg Tab; Drug: Ribociclib 200Mg Oral Tablet; Drug: Abemaciclib 150 MG Oral Tablet

CYP3A4*22/*22

EXPERIMENTAL

This arm will include subjects with CYP3A4\*22/\*22 genotype. They will receive a single oral dose of each CDK4/6 inhibitor on separate days, with at least 6 days and no more than 30 days between each medication. All participants will receive the medications in the same order: Palbociclib, Ribociclib, Abemaciclib Ribociclib- 200 mg tablet Abemaciclib- 150 mg tablet Palbociclib-125 mg tablet PK sampling will be done at the time of drug administration and at different time points until 48 hours post administration.

Drug: Palbociclib 125Mg Tab; Drug: Ribociclib 200Mg Oral Tablet; Drug: Abemaciclib 150 MG Oral Tablet

Interventions

Palbociclib 125Mg Tab DRUG

125 mg single dose

Also known as: ibrance

CYP3A4*1/*1; CYP3A4*1/*22; CYP3A4*22/*22

Ribociclib 200Mg Oral Tablet DRUG

200 mg single dose

Also known as: kisqali

CYP3A4*1/*1; CYP3A4*1/*22; CYP3A4*22/*22

Abemaciclib 150 MG Oral Tablet DRUG

150 mg single dose

Also known as: verzenio

CYP3A4*1/*1; CYP3A4*1/*22; CYP3A4*22/*22

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• MGI participant with genotype of interest (e.g., CYP3A4\*1/\*1, CYP3A4\*1/\*22, or CYP3A4\*22/\*22) and consented to recontact for future research
• Age≥18
• Ability to understand and the willingness to sign a written informed consent.

You may not qualify if:

• Concurrent use of a moderate or strong inhibitor or inducer of CYP3A4, based on the current version of the Drug Interactions Flockhart Table™, available at this link or by google search: https://drug-interactions.medicine.iu.edu/MainTable.aspx
• Carriers another variant known to affect CYP3A4 activity, particularly CYP3A4\*20.
• Active malignancy or other disease state that would affect the pharmacokinetics of CDK4/6 inhibitors or place the participant at particular risk of toxicity from a single dose of a CDK4/6 inhibitor, in the opinion of the study team
• History of allergic reaction to CDK4/6 inhibitor
• Pregnancy or nursing female

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

MeSH Terms

Interventions

palbociclib; ribociclib; Tablets; abemaciclib

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Daniel L Hertz

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: arms are designated based off of genotype; however, treatment is the same for each arm

Study Record Dates

• First Submitted: January 10, 2023
• First Posted: January 20, 2023
• Study Start: March 1, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 2, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share